Idiopathic uveitis is an immunopathogenic disease that can destroy vision by damaging intraocular structures. The cornea, lens, ciliary body, choroid, optic nerve, and retina can be affected by this antigen driven response. The accepted model for this disease in experimental animals is produced by a single injection of a protein antigen into the vitreous cavity. This results in a transient clinical uveitis that recurs with systemic administration of the same antigen at a later time. This uveitis is characterized by the sequestering of immunocompetent lymphocytes in the uvea of the eye. The relative importance of T- and B-lymphocyte subpopulations in the production of this response is currently unknown. This proposal will expand the scope and understanding of T- and B-cell presence in the uvea during primary, secondary, and chronic bovine gamma globulin (BGG) stimulation. We propose to: (1) produce a chronic uveitis with the implantation of a slow-release polymer containing BGG into the suprachoroidal space or into the vitreous cavity; (2) examine T- and B-cell presence and B-cell antibody production in the primary, secondary, and chronic BGG stimulation model, using fluorescein-labeled antipthymocyte and anti-heavy chain antisera and a modification of the Jerne plaque assay; (3) determine the origin of expanding lymphocyte populations in each of these responses to antigen by studying the incorporation of tritiated thymidine into DNA-synthesizing lymphocytes in the spleen or in the uvea, using autoradiography and liquid scintillation techniques; (4) study the response of the uvea to cellular antigen (allogeneic lymphocytes injected intravitreally), using these same techniques and a 51chromium release assay for generated killer lymphocytes; and (5) evaluate the efficacy of Cyclosporin-A, an immunosuppressant drug with minimal systemic side effects and a marked ability to suppress T-cell function and antibody production in man and animals.